STABLE-ICAS: Strategy for Adequate Blood Pressure Lowering in the Patients With Intracranial Atherosclerosis

• Sponsor: Asan Medical Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01104311
• Collaborator: Pfizer (Industry)
• Enrollment: 132
• Locations: 16
• Arms: 2
• Duration (Months): 68
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

To develop adequate blood pressure (BP) lowering strategy after subacute ischemic stroke patients with symptomatic severe intracranial atherosclerosis.

Primary hypothesis of this study is that aggressive BP control (lowering systolic BP between 110mmHg and 120mmHg) will not increase the ischemic lesion volumes in hemisphere compared to modest BP lowering (lowering systolic BP between 130mmHg and 140mmHg) in the patients with symptomatic severe intracranial atherosclerosis.

Condition or Disease	Intervention/Treatment	Phase
Brain Ischemia	Procedure: Aggressive BP lowering; Procedure: modest blood pressure lowering	Phase 4

Detailed Description

The benefits of BP lowering in the prevention of primary and secondary prevention of stroke is established well, although absolute target BP level is uncertain. Current guidelines defined the normal BP as <120/80mmHg and recommend individualized target BP level.

Large well performed stroke prevention trials consistently showed that reduction of 10/5mmHg in patients with systolic BP below 140mmHg had clear benefits in the prevention of cardiovascular events. However, we have a dilemma about BP control in the patients with severe intracranial atherosclerosis.

Aggressive BP control will be more effective in the prevention of overall cardiovascular events than modest BP control, but aggressive BP control will reduce cerebral perfusion in the territory of severe intracranial disease and may increase the risk of ischemic damage.

The study will try to reveal aggressive BP control in the patients with symptomatic severe intracranial atherosclerosis is not increase ischemic lesion volume in hemisphere to compare modest BP control.

Study Design

• Study Type: Interventional
• Actual Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Multicenter Clinical Trial for Development of Guidelines of Adequate Blood Pressure Lowering in the Subacute Ischemic Stroke Patients Due to Intracranial Atherosclerosis
• Study Start Date: Apr 1, 2010
• Actual Primary Completion Date: Apr 1, 2014
• Actual Study Completion Date: Dec 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aggressive BP lowering Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period	Procedure: Aggressive BP lowering; adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level; Other Names: Aggressive BP control
Active Comparator: Modest BP lowering Lowering of systolic blood pressure between 130mmHg and 140mmHg	Procedure: modest blood pressure lowering; adjust the amount and number of antihypertensive drugs; Other Names: Modest BP control

Outcome Measures

Primary Outcome Measures

1. Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI) [Screening to 24 weeks]

   The difference between final ischemic lesions volume and base ischemic lesions of both hemisphere on FLAIR MRI

Secondary Outcome Measures

1. Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population [24 weeks]

   the difference between final ischemic lesions volume and base ischemic lesions in the territory of symptomatic intracranial disease on FLAIR MRI

2. The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI [24 weeks]

3. Number of Participants With Cardiovascular Events From Screening to Week 24 in ITT Population. [24 weeks]

4. Total Number of Cardiovascular Events Form Screening to Week 24 in ITT Population. [24 Week]

5. Number of Participants With Vascular Death From Screening to Week 24 in ITT Population. [24 Weeks]

6. Number of Participants With Adverse Events [24 Weeks]

   Number of Participants with Adverse Events

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• acute symptomatic ischemic stroke having relevant lesion on DWI(Diffusion weighted image) MRI 7 days after and 42 days within onset.

• relevant stenosis(more than 50%) or occlusion from MCA(middle cerebral artery)(M1) to distal of ICA(internal carotid artery ) on MR(Magnetic resonance) angiogram or CT angiogram.

• mean systolic blood pressure>=140mmHg or taking antihypertensive drug on screening.

Exclusion Criteria:

• taking more than 3 antihypertensive drugs and mean systolic blood pressure>=150mmHg on screening.

• history of recent thrombolysis but stenosis or occlusion remained after thrombolysis.

• evidence of orthostatic hypotension

• suspicious embolic cerebrovascular stenosis

• planned state of cerebrovascular surgery or angioplasty or stent 7 months within screening.

• severe stroke-NIHSS>=16

• mean systolic blood pressure>=200mmHg which is not able to control on screening.

• abnormal blood test finding (abnormal LFT(liver function test), anemia, renal insufficiency)

• pregnant or breast-feeding

• severe stroke sequela or medical problem

• suspicious secondary hypertension

• disease causing edema or significant ankle edema on screening.

• severe heart failure which correspond to NYHA (New York Heart Association )heart failure classification class III or IV.

• inappropriate condition determined by investigator

• Patient who do not have FLAIR image on or two months prior to screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Chungnam National University Hospital	Daejeon	Chungnam	Korea, Republic of	301-721
2	Myongji Hospital	Goyang	Gyeonggi-do	Korea, Republic of	412-270
3	Wonkwang University Hospital	Iksan	Jeonbuk	Korea, Republic of	570-711
4	Inje University Pusan Paik Hospital	Busan		Korea, Republic of	614-735
5	Yeungnam University Hospital	Daegu		Korea, Republic of	705-717
6	Eulji University Hospital	Daejon		Korea, Republic of	302-799
7	Kyungpook National University Hospital	Deagu		Korea, Republic of	700-721
8	Chonnam National University Hospital	Gwangju		Korea, Republic of	501-757
9	Inha University Hospital	Inchon		Korea, Republic of	400-103
10	Dong-A University Hospital	Pusan		Korea, Republic of	602-715
11	Kyung Hee University Medical Center	Seoul		Korea, Republic of	130-702
12	Seoul Medical Center	Seoul		Korea, Republic of	135-740
13	Korea University Anam Hospital	Seoul		Korea, Republic of	136-705
14	Asan Medical Center	Seoul		Korea, Republic of	138-736
15	Eulji Hospital	Seoul		Korea, Republic of	139-872
16	Boramae Hospital	Seoul		Korea, Republic of	156-707

Sponsors and Collaborators

• Asan Medical Center
• Pfizer

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sun U. Kwon, department of neurology, Asan Medical Center
• ClinicalTrials.gov Identifier: NCT01104311
• Other Study ID Numbers: STABLE-ICAS
• First Posted: Apr 15, 2010
• Last Update Posted: Mar 7, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Keywords provided by Sun U. Kwon, department of neurology, Asan Medical Center: Blood Pressure; Atherosclerosis; Brain Ischemia
• Additional relevant MeSH terms: Brain Ischemia; Intracranial Arteriosclerosis; Atherosclerosis; Ischemia

Study Results

Participant Flow

Recruitment Details	The recruitment period of this study was from 07/Apr/2010 to 2/Apr/2014 and there had been recruited at medical clinic.
Pre-assignment Detail	There were not any significant events and approaches for the overall study following participant enrollment.

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs
Period Title: Overall Study
STARTED	66	66
COMPLETED	56	54
NOT COMPLETED	10	12

Baseline Characteristics

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering	Total
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs	Total of all reporting groups
Overall Participants	66	63	129
Age, Customized (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.8 (8.5)	63.5 (11.2)	64.2 (9.85)
Gender (Count of Participants)
Female	25 37.9%	27 42.9%	52 40.3%
Male	41 62.1%	36 57.1%	77 59.7%

Outcome Measures

1. Primary Outcome

Title	Ischemic Lesion Volume Change in the Whole Forebrain on Fluid Attenuation Inversion Recovery (FLAIR) Magnetic Resonance Imaging (MRI)
Description	The difference between final ischemic lesions volume and base ischemic lesions of both hemisphere on FLAIR MRI
Time Frame	Screening to 24 weeks

Outcome Measure Data

Analysis Population Description

The Number of Participants Analyzed by FAS(Full analysis)Population. FAS Population (Aggressive BP Lowering: 59, Modest BP Lowering: 52)

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs
Measure Participants	59	52
Screening	11.2 (24.1)	10.4 (19.4)
Week 24	16.1 (39.3)	12.6 (20.0)
Change from Screening to Week 24	4.9 (18.3)	2.2 (8.2)

2. Secondary Outcome

Title	Change of the Ischemic Lesion Volume in Cerebral Hemisphere on FLAIR From Screening to Week 24 in FAS Population
Description	the difference between final ischemic lesions volume and base ischemic lesions in the territory of symptomatic intracranial disease on FLAIR MRI
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The number of participants are analyzed by FAS population.

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs
Measure Participants	59	52
Screening	10.2 (22.6)	9.9 (19.4)
Week 24	15.0 (38.6)	12.0 (20.0)
Change from Screening to Week 24	4.9 (18.3)	2.1 (8.2)

3. Secondary Outcome

Title	The Number of Patients With New Ischemic Lesion in the Whole Forebrain on FLAIR MRI
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The Number of Participants are analyzed by ITT (Intent to treat) Population. ITT Population (Aggressive BP Lowering: 66, Modest BP Lowering: 63)

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs
Measure Participants	66	63
Yes	10 15.2%	5 7.9%
No	49 74.2%	47 74.6%
Missing data	7 10.6%	11 17.5%

4. Secondary Outcome

Title	Number of Participants With Cardiovascular Events From Screening to Week 24 in ITT Population.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

The number of participants are analyzed by ITT Population.

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs
Measure Participants	66	63
Number [participants]	14 21.2%	14 22.2%

5. Secondary Outcome

Title	Total Number of Cardiovascular Events Form Screening to Week 24 in ITT Population.
Time Frame	24 Week

Outcome Measure Data

Analysis Population Description

The number of participants are analyzed by ITT population.

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs
Measure Participants	66	63
Number [events]	17	15

6. Secondary Outcome

Title	Number of Participants With Vascular Death From Screening to Week 24 in ITT Population.
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

The number of participants are analyzed by ITT population.

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs
Measure Participants	66	63
Number [participants]	0 0%	0 0%

7. Secondary Outcome

Title	Number of Participants With Adverse Events
Description	Number of Participants with Adverse Events
Time Frame	24 Weeks

Outcome Measure Data

Analysis Population Description

The number of participants are analyzed by Safety population.

Arm/Group Title	Aggressive BP Lowering	Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level (Safety population: 65)	Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs (Safety population: 65)
Measure Participants	65	65
With at least on AE	51 77.3%	47 74.6%
With at leat one SAE	10 15.2%	8 12.7%
Withdrawn due to AE	1 1.5%	4 6.3%
With AE due to the treatment	5 7.6%	3 4.8%
Who died	0 0%	0 0%

Adverse Events

Arm/Group Title	Aggressive BP Lowering		Modest BP Lowering
Arm/Group Description	Lowering of systolic blood pressure between 110mmHg and 120mmHg during study period Aggressive BP lowering: adjust the amount and number of antihypertensive drugs to lowering of systolic blood pressure to target level (Safety population: 65)		Lowering of systolic blood pressure between 130mmHg and 140mmHg modest blood pressure lowering: adjust the amount and number of antihypertensive drugs (Safety population: 65)
All Cause Mortality
	Aggressive BP Lowering		Modest BP Lowering
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aggressive BP Lowering		Modest BP Lowering
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/65 (15.4%)		8/65 (12.3%)
Gastrointestinal disorders
GASTRIC ULCER HAEMORRHAGIC	0/65 (0%)	0	1/65 (1.5%)	1
General disorders
ASTHENIA	1/65 (1.5%)	1	1/65 (1.5%)	1
Immune system disorders
INFECTION BACTERIAL	1/65 (1.5%)	1	0/65 (0%)	0
Musculoskeletal and connective tissue disorders
FRACTURE	1/65 (1.5%)	1	0/65 (0%)	0
MUSCLE WEAKNESS	0/65 (0%)	0	1/65 (1.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OVARIAN CARCINOMA	0/65 (0%)	0	1/65 (1.5%)	1
COLON CARCINOMA	1/65 (1.5%)	1	0/65 (0%)	0
GENITAL NEOPLASM MALIGNANT MALE	0/65 (0%)	0	1/65 (1.5%)	1
Nervous system disorders
HEADACHE	1/65 (1.5%)	1	0/65 (0%)	0
NEUROPATHY	1/65 (1.5%)	1	0/65 (0%)	0
DIZZINESS	2/65 (3.1%)	2	1/65 (1.5%)	2
STUPOR	0/65 (0%)	0	1/65 (1.5%)	1
Psychiatric disorders
DELIRIUM	1/65 (1.5%)	1	0/65 (0%)	0
Renal and urinary disorders
PYELONEPHRITIS	0/65 (0%)	0	1/65 (1.5%)	1
Vascular disorders
CEREBRAL INFARCTION	0/65 (0%)	0	1/65 (1.5%)	1
TRANSIENT ISCHAEMIC ATTACK	1/65 (1.5%)	1	0/65 (0%)	0
Other (Not Including Serious) Adverse Events
	Aggressive BP Lowering		Modest BP Lowering
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/65 (78.5%)		47/65 (72.3%)
Blood and lymphatic system disorders
LEUCOPENIA	0/65 (0%)	0	1/65 (1.5%)	1
GINGIVAL BLEEDING	1/65 (1.5%)	1	0/65 (0%)	0
PURPURA	2/65 (3.1%)	3	0/65 (0%)	0
Cardiac disorders
ANGINA PECTORIS	1/65 (1.5%)	1	0/65 (0%)	0
Ear and labyrinth disorders
TINNITUS	1/65 (1.5%)	1	0/65 (0%)	0
Eye disorders
BLEPHARITIS	1/65 (1.5%)	1	0/65 (0%)	0
Gastrointestinal disorders
VOMITING	2/65 (3.1%)	3	0/65 (0%)	0
CONSTIPATION	4/65 (6.2%)	4	3/65 (4.6%)	3
ABDOMINAL PAIN	1/65 (1.5%)	1	0/65 (0%)	0
DIARRHOEA	3/65 (4.6%)	3	2/65 (3.1%)	3
DYSPEPSIA	2/65 (3.1%)	2	2/65 (3.1%)	2
NAUSEA	1/65 (1.5%)	1	2/65 (3.1%)	3
GASTRIC ULCER	1/65 (1.5%)	1	0/65 (0%)	0
GASTRITIS	0/65 (0%)	0	1/65 (1.5%)	1
GASTROENTERITIS	0/65 (0%)	0	1/65 (1.5%)	1
GASTRIC ULCER HAEMORRHAGIC	0/65 (0%)	0	1/65 (1.5%)	1
PERIODONTAL DISORDERS	0/65 (0%)	0	1/65 (1.5%)	1
PERIODONTAL DESTRUCTION	2/65 (3.1%)	2	0/65 (0%)	0
MELAENA	1/65 (1.5%)	1	1/65 (1.5%)	1
General disorders
C-REACTIVE PROTEIN INCREASED	1/65 (1.5%)	1	1/65 (1.5%)	1
CHEST PAIN	3/65 (4.6%)	3	1/65 (1.5%)	1
OEDEMA PERIPHERAL	3/65 (4.6%)	3	4/65 (6.2%)	4
ASTHENIA	1/65 (1.5%)	1	2/65 (3.1%)	2
ABDOMEN ENLARGED	1/65 (1.5%)	1	0/65 (0%)	0
SYNCOPE	0/65 (0%)	0	1/65 (1.5%)	1
ALLERGIC REACTION	1/65 (1.5%)	1	0/65 (0%)	0
FEVER	2/65 (3.1%)	2	1/65 (1.5%)	1
OEDEMA GENERALISED	0/65 (0%)	0	1/65 (1.5%)	1
FATIGUE	1/65 (1.5%)	1	1/65 (1.5%)	1
AMNESIA	0/65 (0%)	0	1/65 (1.5%)	1
INSOMNIA	2/65 (3.1%)	2	3/65 (4.6%)	3
ANXIETY	1/65 (1.5%)	1	1/65 (1.5%)	1
DELIRIUM	2/65 (3.1%)	2	0/65 (0%)	0
ANOREXIA	2/65 (3.1%)	2	1/65 (1.5%)	1
DEPRESSION	4/65 (6.2%)	4	5/65 (7.7%)	5
Hepatobiliary disorders
HEPATIC ENZYMES INCREASED	2/65 (3.1%)	2	2/65 (3.1%)	2
GALLBLADDER DISORDER	0/65 (0%)	0	1/65 (1.5%)	1
BILIRUBINAEMIA	1/65 (1.5%)	1	0/65 (0%)	0
Immune system disorders
ABSCESS	0/65 (0%)	0	1/65 (1.5%)	1
HERPES ZOSTER	1/65 (1.5%)	1	0/65 (0%)	0
INFECTION BACTERIAL	1/65 (1.5%)	1	0/65 (0%)	0
Metabolism and nutrition disorders
HYPERTRIGLYCERIDAEMIA	1/65 (1.5%)	1	0/65 (0%)	0
HYPERLIPAEMIA	1/65 (1.5%)	1	1/65 (1.5%)	1
DIABETES MELLITUS	2/65 (3.1%)	2	1/65 (1.5%)	1
HYPOGLYCAEMIA	1/65 (1.5%)	2	0/65 (0%)	0
Musculoskeletal and connective tissue disorders
SKELETAL PAIN	0/65 (0%)	0	1/65 (1.5%)	1
FRACTURE	1/65 (1.5%)	1	1/65 (1.5%)	1
ARTHRITIS	0/65 (0%)	0	1/65 (1.5%)	1
ARTHRALGIA	4/65 (6.2%)	4	1/65 (1.5%)	1
MUSCLE WEAKNESS	1/65 (1.5%)	3	2/65 (3.1%)	3
MYALGIA	1/65 (1.5%)	1	0/65 (0%)	0
ROTARY CUFF SYNDROME	0/65 (0%)	0	1/65 (1.5%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
OVARIAN CARCINOMA	0/65 (0%)	0	1/65 (1.5%)	1
COLON CARCINOMA	1/65 (1.5%)	1	0/65 (0%)	0
GENITAL NEOPLASM MALIGNANT MALE	0/65 (0%)	0	1/65 (1.5%)	1
Nervous system disorders
PARAESTHESIA	3/65 (4.6%)	3	2/65 (3.1%)	2
HYPOAESTHESIA	1/65 (1.5%)	1	2/65 (3.1%)	2
HEADACHE	8/65 (12.3%)	10	12/65 (18.5%)	13
PARALYSIS	1/65 (1.5%)	1	0/65 (0%)	0
NEUROPATHY PERIPHERAL	0/65 (0%)	0	1/65 (1.5%)	1
DYSPHONIA	0/65 (0%)	0	1/65 (1.5%)	1
GAIT ABNORMAL	1/65 (1.5%)	1	0/65 (0%)	0
VISUAL FIELD DEFECT	1/65 (1.5%)	1	0/65 (0%)	0
NEUROPATHY	1/65 (1.5%)	1	0/65 (0%)	0
APHASIA	1/65 (1.5%)	1	0/65 (0%)	0
PTOSIS	1/65 (1.5%)	1	0/65 (0%)	0
DIZZINESS	9/65 (13.8%)	9	11/65 (16.9%)	11
SPEECH DISORDER	1/65 (1.5%)	1	0/65 (0%)	0
COGNITIVE DISORDERS	1/65 (1.5%)	1	1/65 (1.5%)	1
DEMENTIA	0/65 (0%)	0	3/65 (4.6%)	3
APRAXIA	1/65 (1.5%)	1	0/65 (0%)	0
STUPOR	1/65 (1.5%)	1	2/65 (3.1%)	2
Renal and urinary disorders
RENAL FAILURE CHRONIC	1/65 (1.5%)	1	0/65 (0%)	0
BLADDER CALCULUS	1/65 (1.5%)	1	0/65 (0%)	0
MICTURITION DISORDER	1/65 (1.5%)	1	0/65 (0%)	0
MICTURITION FREQUENCY	0/65 (0%)	0	1/65 (1.5%)	1
PYELONEPHRITIS	0/65 (0%)	0	1/65 (1.5%)	1
NOCTURIA	1/65 (1.5%)	1	0/65 (0%)	0
FACE OEDEMA	1/65 (1.5%)	1	1/65 (1.5%)	1
HAEMATURIA	0/65 (0%)	0	1/65 (1.5%)	1
Reproductive system and breast disorders
PROSTATIC HYPERPLASIA	0/65 (0%)	0	1/65 (1.5%)	1
AZOTAEMIA	1/65 (1.5%)	1	0/65 (0%)	0
Respiratory, thoracic and mediastinal disorders
COUGHING	3/65 (4.6%)	3	2/65 (3.1%)	3
RHINITIS	0/65 (0%)	0	1/65 (1.5%)	1
UPPER RESPIRATORY TRACT INFECTIO	2/65 (3.1%)	2	0/65 (0%)	0
PHARYNGITIS	1/65 (1.5%)	1	4/65 (6.2%)	4
EPISTAXIS	1/65 (1.5%)	1	1/65 (1.5%)	1
PNEUMONIA	0/65 (0%)	0	1/65 (1.5%)	1
DYSPNOEA	1/65 (1.5%)	1	0/65 (0%)	0
Skin and subcutaneous tissue disorders
PRURITUS	1/65 (1.5%)	1	0/65 (0%)	0
URTICARIA	1/65 (1.5%)	1	0/65 (0%)	0
RASH	0/65 (0%)	0	1/65 (1.5%)	1
ECZEMA	1/65 (1.5%)	1	0/65 (0%)	0
OTITIS EXTERNA	0/65 (0%)	0	1/65 (1.5%)	1
DERMATITIS CONTACT	0/65 (0%)	0	1/65 (1.5%)	1
DERMATITIS FUNGAL	0/65 (0%)	0	1/65 (1.5%)	3
SKIN EXFOLIATION	1/65 (1.5%)	1	0/65 (0%)	0
Vascular disorders
HYPERTENSION AGGRAVATED	0/65 (0%)	0	1/65 (1.5%)	1
HYPOTENSION POSTURAL	1/65 (1.5%)	1	0/65 (0%)	0
CEREBRAL INFARCTION	1/65 (1.5%)	1	1/65 (1.5%)	1
RENAL ARTERY OCCLUSION	1/65 (1.5%)	1	0/65 (0%)	0
TRANSIENT ISCHAEMIC ATTACK	1/65 (1.5%)	1	0/65 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.